Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney

Cell Rep. 2015 Aug 25;12(8):1325-38. doi: 10.1016/j.celrep.2015.07.034. Epub 2015 Aug 13.


After acute kidney injury (AKI), surviving cells within the nephron proliferate and repair. We identify Sox9 as an acute epithelial stress response in renal regeneration. Translational profiling after AKI revealed a rapid upregulation of Sox9 within proximal tubule (PT) cells, the nephron cell type most vulnerable to AKI. Descendants of Sox9(+) cells generate the bulk of the nephron during development and regenerate functional PT epithelium after AKI-induced reactivation of Sox9 after renal injury. After restoration of renal function post-AKI, persistent Sox9 expression highlights regions of unresolved damage within injured nephrons. Inactivation of Sox9 in PT cells pre-injury indicates that Sox9 is required for the normal course of post-AKI recovery. These findings link Sox9 to cell intrinsic mechanisms regulating development and repair of the mammalian nephron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Animals
  • Cell Lineage
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Mice
  • Nephrons / cytology
  • Nephrons / metabolism
  • Re-Epithelialization*
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Transcriptional Activation*
  • Up-Regulation


  • SOX9 Transcription Factor
  • Sox9 protein, mouse